One of anodynes which have been recently developed is an enkephalinase inhibitor. The structure of such an enkephalinase inhibitor contains a moiety derived from 2-aralkyl-3-acetylthiopropionic acid. It has been known that enkephalinase inhibitors exert different pharmacological actions depending on the steric structure of the aralkyl group in the 2-position. It has also been known that enkephalinase inhibitors having an aralkyl group in (S) configuration exert effective pharmacological actions.
An example of the process for the preparation of a (S)-2-aralkyl-3-acetylthiopropionic acid is an optical resolution method with ephedrine as disclosed in JP-A-2-161 (The term "JP-A" as used herein means an "unexamined published Japanese patent application").
However, the optical resolution method which comprises directly obtaining a (S)-2-aralkyl-3-acetylthiopropionic acid is disadvantageous in that a very expensive optical resolution agent must be used.
On the other hand, one possible 2-aralkyl-3-acetylthiopropionic acid precursors is a 2-aralkyl-3-halogenopropionic acid. An example of the process for the preparation of an optically active 2-aralkyl-3-halogenopropionic acid is a process for the preparation of a (R)-2-benzyl-3-chloropropionic acid and the methyl ester thereof as disclosed in K. Haaf et al., Chemische. Berichte, 123 (1990), pp. 635-638. In the preparation process disclosed in this reference, L-phenylalanine is processed in 7 stages including high temperature rearrangement reaction and 10 enzymatic reaction with lipase derived from pig liver to synthesize a (R)-2-benzyl-3-chloropropionic acid.
However, the product is not in (S)-configuration and is produced through complicated steps.
As the process for the preparation of a (S)-2-aralkyl-3-acetylthiopropionic acid or (R)-2-aralkyl-3-chloropropionic acid as an intermediate of an enkephalinase inhibitor there have been known the foregoing processes. However, these processes are not industrially satisfiable because they require a multi-stage reaction and expensive reagents.